L. crude polysaccharide meditated synbiotic fermented whey beverage ameliorates hypobaric hypoxia induced intestinal damage.

Hypobaric hypoxia causes oxidative stress and inflammatory responses and disrupts the gut microbiome and metabolome. In this study, we developed a synbiotic fermented whey beverage, combining kefir and L. crude polysaccharides, to explore its protective effects against high-altitude induced injury in mice. The beverage, formulated with 0.8% (w/v) polysaccharides and kefir inoculation, demonstrated robust fermentation parameters and antioxidative capacity. When applied to a hypobaric hypoxia mouse model, the synbiotic fermented whey significantly reduced oxidation and protected the intestinal barrier by lowering inflammation, protecting the intestinal structure, increasing goblet cell counts, and reducing apoptosis. It also modulated the gut microbiota, enriching beneficial taxa as and , while reducing harmful ones like and , and enhancing short-chain fatty acid (SCFA) production. Notably, the beverage increased berberine and nicotinic acid levels, activating the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway and influencing nicotinate and nicotinamide metabolites linked to the suppression of , thereby alleviating intestinal inflammation and barrier damage. These effects contributed to the alleviation of hypoxia-induced intestinal damage in mice. This study highlights the potential of synbiotics and whey fermentation in novel nutritional interventions in high altitude environments.